1. Field of the Invention
This invention relates to a novel and efficient process for making 1-(3-benzyloxyphenyl)-1,1-dimethylheptane, a valuable intermediate for syntheses of 2-(cyclic- and acyclic-substituted)-5-(1,1-dimethylheptyl)phenols useful as analgesic agents as is described in U.S. Pat. Nos. 4,285,867 and 4,284,829, issued Aug. 25, 1981 and Aug. 18, 1981, respectively. More specifically it comprises methylation of 1-(3-benzyloxyphenyl)-1-chloro-1-methylheptane by means of trimethylaluminum. Said chloroheptane reactant is prepared by chlorination with hydrogen chloride of 1-(3-benzyloxyphenyl)-1-methylheptan-1-ol, itself prepared by reaction of n-hexylmagnesium bromide with 3-benzyloxyphenylacetophenone which in turn is prepared by benzylation of 3-hydroxyacetophenone.
2. Description of the Prior Art
The reaction of trialkylaluminums with chlorohydrocarbons is reported by Miller in J. Org. Chem. 31, 908-912 (1966), by Kennedy, J. Org. Chem. 35, 532 (1970), and by references cited therein. Miller notes that of the reactions of halohydrocarbons with alkylaluminums, the preparation of alkylbenzenes by alkylation to (alpha- and beta-haloalkyl)benzenes is the most promising from a synthetic standpoint.
Until the present invention, 1-(3-benzyloxyphenyl)-1,1-dimethylheptane was prepared from methyl 3-hydroxybenzoate as described in U.S. Pat. No. 4,285,867, issued Aug. 25, 1981. The overall sequence comprised benzylation of the phenolic group to produce methyl 3-benzyloxybenzoate followed by reaction of said ether ester with methyl magnesium iodide to give 3-benzyloxybenzene-2-propanol. Reaction of the thus-produced propanol derivative with hydrochloric acid afforded 2-(3-benzyloxyphenyl)-2-chloropropane which was then reacted with n-hexylmagnesium bromide to provide 1-(3-benzyloxyphenyl)-1,1-dimethylheptane.